Prior work suggests that psychological resilience to trauma may protect not only mental but also physical health. This study examined the relationship of prepandemic psychological resilience to lifetime trauma with self-reported COVID-19 infection and symptoms during the early years of the COVID-19 pandemic. Data are from 18,670 longitudinal cohort participants in the Nurses' Health Study II. Based on prior evidence that trauma and subsequent distress can increase infection risk and severity, and that psychological assets may offset this risk, we hypothesized higher versus lower psychological resilience to prior trauma would be associated with lower risk for COVID-19 infection. Prepandemic resilience was assessed via self-report between 2017 and 2019 based on self-reported lifetime trauma exposure and psychological health. COVID-19 infection and symptoms were self-reported on seven questionnaires administered between May 2020 and October 2021, from which we derived a composite outcome measure of probable COVID-19 infection, defined as having 3+ COVID-19 symptoms (out of 9) and/or a positive COVID-19 test result at any single assessment. Multivariable regression revealed significant associations between higher prepandemic resilience scores and lower risk for probable COVID-19 infection, adjusting for sociodemographic and COVID-19-related risk factors (risk ratio [RR] = 0.90 [95% confidence interval {CI}, 0.87-0.93]). Considering subcomponents of the composite COVID-19 infection measure separately, prepandemic resilience was significantly associated with lower risk of reported symptoms (RR = 0.83 [95% CI, 0.79-0.88]), but not with a positive test result alone (RR = 0.96 [95% CI, 0.91-1.01]). Identifying protective factors for infection risk may help inform psychosocial interventions to improve health outcomes.